Dibutyryl cyclic AMP (DBCAMP) stimulates, inhibits or has no effect on mitosis depending upon the phenotype of the cell involved. This suggests that CAMP is not directly involved in regulation of mitosis itself but of other processes which secondarily effect cell division. DBCAMP has, however, a considerable effect on the morphology of transformed fibroblasts and on cells whose morphology is altered by Colchicine or Vinblastine. The antagonism between Colchicine and DBCAMP suggests that microtubules bay be involved; however considerable evidence exists that Colchicine binding proteins (CBP) may be part of cell membranes and it is possible that they are the site of DBCAMP activity and regulation of cell division in some cells. Colchicine has been reported to stimulate DNA synthesis in contact inhibited cells and in plant meristems. Protein kinase (PK) activity of microtubules has been reported to be similar in ion requirements to membrane bound PK rather than to soluble PK. We will investigate colchicine stimulation of DNA synthesis in several contact inhibited lines and strains of cells by autoradiographic and bulk extraction techniques, incorporation of phosphate into cell membranes in inhibited and stimulated cells both in vivo and in isolated membranes (using endogenous and exogenous PK) investigate membrane bound CBP and its states of phosphorylation under stimulated and inhibited conditions, attempt to isolate this protein from membranes using detergents or thermal means and in general compare soluble microtubule protein (which can be polymerized by Weisenberg's techniques) with membrane bound CBP. It is possible that membrane bound PK is related to or identical to membrane bound CBP. Since adenyl cyclase (AC) is a membrane bound protein and some cellular CAMP phosphodiesterases (PD) are membrane bound, the possibility exists that a macromolecular comple of AC, PD and PK exists which can be regulated by a receptor site and that colchicine may modify the activity of the complex. The response of a cell to CAMP may then depend upon the type membrane sites available for phosphor@lation by the complex.